LEISHMANIA
World Class Parasites VOLUME 4 Volumes in the World Class Parasites book series are written for researchers, students and scholars who enjoy reading about excellent research on problems of global significance. Each volume focuses on a parasite, or group of parasites, that has a major impact on human health, or agricultural productivity, and against which we have no satisfactory defense. The volumes are intended to supplement more formal texts that cover taxonomy, life cycles, morphology, vector distribution, symptoms and treatment. They integrate vector, pathogen and host biology and celebrate the diversity of approach that comprises modem parasitological research. Series Editors Samuel J. Black, University of Massachusetts, Amherst, MA, US.A. J. Richard Seed, University of North Carolina, Chapel Hill, NC, US.A.
LEISHMANIA edited by Jay P. Farrell University of Pennsylvania. SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Library of Congress Cataloging-in-Publication Data Leishmania / edited by Jay P. Farrell p. cm. -(World c1ass parasites ; v. 4) Includes bibliographical references and index. ISBN 978-1-4613-5322-5 ISBN 978-1-4615-0955-4 (ebook) DOI 10.1007/978-1-4615-0955-4 1. Leishmaniasis. 2. Leishmania. 1. Farrell, 1. (Jay) II. Series. RCI53.L45 2002 61 6.9'364-dc2 1 2002025496 Copyright 2002 by Springer Science+Business Media New York Originally published by Kluwer Academic Publishers in 2002 Softcover reprint ofthe hardcover lst edition 2002 AII rights reserved. No part ofthis work may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without the written permission from the Publisher, with the exception of any material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work Permission for books published in Europe: permissions@wkap.n\ Permissions for books published in the United States of America: permissions@wkap.com Printed an acid-free paper. Tlte Publisher offers discounts on tltis bookfor course use and bulk purchases. For further information, selld email lo<joanne.tracy@wkap.com>.
'fable OF CONTENTS Preface... Vll CURRENT STATUS OF EPIDEMIOLOGY OF LEISHMANIASES Jean-Pierre Dedet.................................................................. 1 NEW WORLD LEISHMANIASIS: THE ECOLOGY OF LEISHMANIASIS AND THE DIVERSITY OF LEISHMANIAL SPECIES IN CENTRAL AND SOUTH AMERICA. Jeffrey 1. Shaw... 11 PHLEBOTOMINE SAND FLIES: BIOLOGY AND CONTROL Robert Killick-Kendrick... 33 CANINE RESERVOIRS AND LEISHMANIASIS: EPIDEMIOLOGY AND DISEASE. Lenea Maria Carnpino... 45 THE JOURNEY OF LEISHMANIA PARASITES WITHIN THE DIGESTIVE TRACT OF PHLEBOTOMINE SAND FLIES Shaden Kamhawi... 59 MEMBRANE TRANSPORT AND METABOLISM IN LEISHMANIA PARASITES Scott M. Landfear...,... '"... 75 THE INTERACTION OF LEISHMANIA SPP. WITH PHAGOCYTIC RECEPTORS ON MACROPHAGES: THE ROLE OF SERUM OPSONINS David M. Mosser and Andrew Brittingham... 89 LEISHMANIA INFECTION AND MACROPHAGE FUNCTION Greg Matlashewski... 105
CLINICAL AND LABORATORY ASPECTS OF LEISHMANIA CHEMOTHERAPY IN THE ERA OF DRUG RESISTANCE Dan Zilberstein and Moshe Ephros... 115 THE IMMUNOLOGY OF VISCERAL LEISHMANIASIS: CURRENT STATUS Paul M. Kaye... 0",... '"............... 137 THE IMMUNOLOGY OF CUTANEOUS LEISHMANIASIS: EXPERIMENTAL INFECTIONS AND HUMAN DISEASE Jay P. Farrell... '"... 151 ANTI-LEISHMANIA VACCINE Antonio Campos-Neto... 169 Index... '"... 191
PREFACE Parasites of the genus Leishmania are dimorphic protozoans that exist as intracellular amastigotes within mammalian mononucular phagocytes and as flagellated promastigotes within sand fly vectors. Although various species of Leishmania can infect a variety of hosts, the primary importance of these parasites is ability to produce disease in humans and dogs. Human leishmaniasis occurs in tropical, sub-tropical and temperate regions of the world with an estimated 1.5 to 2 million new cases each year. Continued research efforts have markedly increased our understanding of the ecology, epidemiology, and immunology of this disease and recent efforts have dramatically enhanced our knowledge of the cell and molecular biology of leishmanial parasites. However, we are still a long way from controlling this important disease. This book comprises a series of chapters by authors who have devoted their research efforts to the study of Leishmania and leishmaniasis. Transmission and control are covered in the first four chapters with Jean Pierre Dedet starting us off by reviewing the current worldwide epidemiology of leishmaniasis and pointing out the increasing problems associated with HIV-Leishmania co-infection. Next, Jeffrey Shaw discusses the incredible diversity of New World leishmanial species and the ecology of these parasites and their reservoir hosts. Robert Killick-Kendrick then takes up the biology of the sand fly and reviews methods to control transmission of infection to humans and important reservoir hosts such as the dog. Finally, Leana Campino discusses canine leishmaniasis, a topic central to understanding the transmission of human infection since dogs are important reservoir hosts for several species of Leishmania, especially those causing visceral disease. The next several chapters focus on topics of a more experimental nature. The biology of promastigote development within sand flies and the biochemistry of parasite molecules that influence life in the sand fly intestine are covered by Shaden Kamhani. This has been an area of intense study since the discovery that leishmanial lipophosphoglycan mediates attachment pf promastigotes to sand fly gut epithelial cells. Another area impacted by molecular technology is reseach on the metabolic biochemistry of leishmanial parasites and Scott Landfear uses one aspect of parasite metabolism, namely the nature and regulation of membrane transporters, to discuss our understanding of the cell biology of these parasites. The interaction of Leishmania with host macrophages in the topic of the next two chapters. David Mosser and Andrew Brittingham focus on the interaction of parasite molecules and host cell receptors that mediate entry into macrophages and discuss how opsonization by antibody may promote the production of cytokines that promote parasite survival.
Vlll Greg Matlashewski takes a different tack and discusses how infection with different leishmanial species alters macrophage gene expression and signaling pathways. Dan Zilberstein and Moshe Ephros then cover an area critical to the control of leishmaniasis, namely chemotherapy. In addition to reviewing existing drug therapies, they discuss the current understanding of the modes of drug action and mechanisms of drug resistance. The final three chapters are devoted to the immune response to leishmanial infections. Paul Kaye discusses the current state of knowledge of the immune response to human visceral leishmaniasis and relates it to insights gathered from studies of L. donovani in experimental models while I take a similar approach to cover the topic of immunity to human and murine cutaneous leishmaniasis. Finally, Antonio Campos-Neto reviews, in depth, the experimental basis of vaccine development and discusses recent efforts to move experimental vaccines from the laboratory to the field. Leishmaniasis is a complex of infections caused by multiple leishmanial species that cause diverse forms of clinical disease. Each of these species has it own sand fly vectors and reservoir hosts and the ecological aspects that affect their transmission varies enormously. Thus, not all aspects of leishmaniasis are covered in this small volume. For example, little space is devoted to diagnosis and the clinical aspects of infection are only discussed in passing. However, these topics are detailed in multiple texts on clinical tropical medicine. Also missing is a discussion of a newly emerging area that will have enormous impact on our understanding of the biology of Leishmania, namely the Leishmania genome project. A number of laboratories are part of the Leishmania genome network and are actively sequencing leishmanial genes as well as pursuing the development and application of proteomics to complement these sequencing activities. As data continues to emerge from this effort, researchers will have exciting new tools to help tackle both clinical and experimental problems relevant to understanding and controlling this important infectious disease. We can only hope so since, as Professor Dedet concludes in his chapter about our current ability to control leishmaniasis, "there is much still to be done. " Jay P. Farrell, January 2002